Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, USA.

Abstract

BACKGROUND:

Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment.

OBJECTIVE:

DESIGN:

Post hoc analysis.

SETTING:

A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo.

MAIN OUTCOME MEASURES:

RESULTS:

T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change.

CONCLUSIONS:

Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.

Placement and shape of regions of interest (ROIs) used to measure T2-intensities. CSF=cerebrospinal fluid, PU=putamen, AT=anterior thalamus, PT=posterior thalamus, GP=globus pallidus, HC=head of caudate, RN=red nucleus, DT=dentate nucleus. ROIs 5 mm in diameter were placed in the HC, and in AT and PT. ROIs 2 mm in diameter were placed in RN. The PU was traced manually and GP and DT were traced by an edge finding seed-growing technique. Care was taken to avoid inclusion of small hyperintensities, such as lesions or perivascular spaces, within ROIs.